胃食管反流病与胆石症因果关系的孟德尔随机化分析OA

Objective To explore the bidirectional causal relationship between gastroesophageal reflux disease(GERD)and gallstone disease using Mendelian randomization(MR)approach.Methods Instrumental variables—single nucleotide polymorphisms(SNPs)—were obtained from public Genome-Wide Association Study(GWAS)databases,and two-sample bidirectional MR analyses were performed mainly by the inverse variance weighted(IVW)method.MR-PRESSO test,Cochran's Q test,MR-Egger regression intercept test,and leave-one-out analysis were used for sensitivity analysis to assess the reliability and stability of the study results.Subsequently,MR analysis was repeated after adjusting for the effects of different confounding factors to validate the results.The GERD data were sourced from the IEU OpenGWAS project,comprising a total of 602 604 samples(129 080 cases and 473 524 controls).The gallstone disease data were obtained from the FinnGen Biobank,comprising a total of 214 167 samples(19 023 cases and 195 144 controls).Results The results by using the IVW method indicated a causal effect of GERD on gallstone disease(OR=1.472,95%CI:1.326-1.634,P=3.688×10-13),and also a causal effect of gallstone disease on GERD(OR=1.048,95%CI:1.027-1.069,P=5.791×10-6).After adjusting for confounding factors,the results by IVW method showed that the positive association risk of GERD on gallstone disease still remained(OR=1.407,95%CI:1.211-1.635,P=7.948×10-6),and the positive association risk of gallstone disease on GERD also remained(OR=1.052,95%CI:1.029-1.075,P=3.316×10-6).The analysis results using MR-Egger regression intercept test results indicated no evidence of horizontal pleiotropy among the included instrumental variables.The results by leave-one-out analysis suggested that no single SNP that could significantly affect the results.Conclusion MR analysis supports a bidirectional causal relationship between GERD and gallstone disease.